Kiyoshi Nakatsuka

The University of Sheffield, Sheffield, England, United Kingdom

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Publications (88)207.85 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to clarify the effects of 2-year treatment with raloxifene on the proximal femoral geometry among Japanese patients with osteoporosis by hip structure analysis. One hundred ninety-eight community-dwelling postmenopausal women with osteoporosis were enrolled. The structural variables were areal bone mineral density (BMD), cross-sectional area (CSA), section modulus (index of resistance to bending forces), and buckling ratio (index of cortical instability). BMD, CSA, and section modulus at the narrow neck significantly increased by 1.27, 2.67, and 3.90% at 2 years, respectively. BMD, CSA, and section modulus at the intertrochanter significantly increased by 2.55, 4.49, and 6.60% at study termination, respectively. The buckling ratio at the intertrochanter decreased by 2.36% at 1 year, but differences at 2 years became non-significant. Parameters at the shaft were qualitatively similar to those of the narrow neck and intertrochanter. The percent change of the section modulus was significantly higher than that of BMD at 2 years in all three regions. The percent changes of the section modulus is strongly correlated with the percent changes of BMD and CSA, and negative correlated with the percent changes of buckling ratio in all regions. In conclusion, Japanese osteoporotic women on raloxifene therapy have significant improvements of both BMD and geometry in the proximal femur.
    Journal of Bone and Mineral Metabolism 03/2010; 28(5):561-7. DOI:10.1007/s00774-010-0164-5 · 2.46 Impact Factor
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    ABSTRACT: We compared the effects of three different regimens of intravenous clodronate in a retrospective study of 60 patients with Paget disease. A total dose of 1500 mg of clodronate was given as 300 mg for 5 consecutive days (n = 20), 1500 mg as a single infusion (n = 20), or 300 mg as a single infusion for 5 consecutive months (n = 20). The response to treatment and the duration of the effect were assessed from sequential changes in the activity of serum alkaline phosphatase. Treatment with clodronate induced a significant response in 85% of patients. The response rate was comparable in patients treated with 5 daily infusions (90%), with a single infusion (75%), and with 5 monthly infusions (90%). The median duration of response from the start of treatment was 11 months for those treated with five daily infusions and 12 months for the other two regimens. At one year, 22, 40, and 44% of patients had maintained their response in the daily, single, and monthly infusion regimen, respectively (NS). Six patients (32%) treated with 5 daily infusions achieved a remission (complete response) compared with 3 patients treated with a single infusion and 5 monthly infusions, respectively (16 and 15% respectively, NS). Patients attaining a complete response had a significantly longer duration of response compared with partial responders (median time 15.0 versus 11.5 months, respectively, p < 0.05). We conclude that intravenous clodronate (total dose 1500 mg) suppresses disease activity in the majority of patients with Paget disease of bone. The degree and duration of response were similar for the three regimens. Thus, in the treatment of Paget disease, the choice of regimen is a matter of convenience.
    Journal of Bone and Mineral Research 02/2009; 11(2):178-82. DOI:10.1002/jbmr.5650110206 · 6.83 Impact Factor
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    Philip L Riches · Yasuo Imanishi · Kiyoshi Nakatsuka · Stuart H Ralston ·
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    ABSTRACT: Early-onset familial Paget disease of bone (EoPDB) is a rare condition caused by a 27-bp insertion mutation affecting the signal peptide of TNFRSF11A, which encodes RANK. EoPDB shows phenotypic overlap to both familial expansile osteolysis and expansile skeletal hyperphosphatasia, which are caused by similar mutations in TNFRSF11A. Although EoPDB is characterized by elevated bone turnover, there is no published information on the response of this condition to antiresorptive therapy. Here, we describe the clinical and biochemical response to bisphosphonate therapy in three patients with EoPDB. In all cases, treatment with the first-generation bisphosphonate etidronate at high doses reduced biochemical markers of bone turnover but the response was incomplete and short-lived. In contrast, treatment with aminobisphosphonates resulted in greater suppression of biochemical markers of bone turnover with an extended duration of response. From a clinical perspective, the results were less impressive and there was no clear benefit from antiresorptive treatment in terms of bone deformity, deafness, and tooth loss, although bone pain improved in one patient. We conclude that intravenous aminobisphosphonate therapy may be the preferred mode of treatment for EoPDB to provide long-term suppression of bone turnover. The long-term clinical effects of treatment on the natural history of the bone disease remain uncertain however, and this will require further study.
    Calcified Tissue International 11/2008; 83(4):272-5. DOI:10.1007/s00223-008-9177-7 · 3.27 Impact Factor
  • Kiyoshi Nakatsuka · Yoshiki Nishizawa · Masakazu Miura ·
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    ABSTRACT: Propeptides of type I procollagen are generated during the process of collagen formation in bone matrix. Among them measurements of circulating N-terminal propeptide (PINP) has been recognized as one of promising metabolic bone markers in the assessment of efficacy of pharmaceutical intervention for osteoporosis. Recently assays of PINP have been established to be supplied as measurement kits following those of C-terminal propeptide (PICP) and clinical data on usefulness of PINP in the evaluation of teriparatide an anabolic agent as well as various anti-catabolic agents have accumulated. Therefore, the measurement of PINP must be an essential tool in Japan at the time when newer agents for osteoporosis are applied to clinical practice in the future.
    Clinical calcium 07/2006; 16(6):977-85.
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    ABSTRACT: We here propose guidelines for the diagnosis and management of Paget's disease of bone (PDB) in Japan. These guidelines provide basic information on the epidemiology, pathophysiology, clinical signs and symptoms, diagnosis, indications for treatment, and available therapy, including orthopedic surgery. PDB is a chronic disorder characterized by focal abnormalities of bone turnover. The characteristic feature of PDB is excessive osteoclastic bone resorption coupled to increased and disorganized bone formation. The most common symptom of PDB is pain in involved bones. The most serious complication of PDB is malignant bone or soft-tissue tumor. PDB is uncommon in Japan; our survey in 2003 found 169 patients with PDB. The prevalence of PDB in Japan is 0.15/100 000; in patients aged 55 years or more, the proportion reaches 0.41/100 000. A careful medical history and physical examination are essential for the diagnosis. The diagnosis of PDB is based on finding the typical features on radiographs. Bone scintigraphy and measurement of serum alkaline phosphatase are sensitive means of screening for PDB. Since PDB is a rare disease in Japan, bone biopsy is quite often used to exclude bone metastases. The only evidence-based indication for treatment of PDB is pain in involved bones. In Japan, etidronate and calcitonin are approved by the Ministry of Health, Labour and Welfare for treating PDB, but currently risedronate is also under development for treating PDB in Japan. Indications for surgical intervention in PDB include unstable fractures, osteoarthritis, malignant soft-tissue tumor, osteosarcoma, and bone deformity.
    Journal of Bone and Mineral Metabolism 02/2006; 24(5):359-67. DOI:10.1007/s00774-006-0696-x · 2.46 Impact Factor
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    ABSTRACT: The present study aimed to evaluate the prevalence and clinical presentation of Paget's disease of bone (PDB) in Japan. As PDB is a very rare disease in Japan, a nationwide mail survey was conducted targeting doctors in the specialty most frequently diagnosing and treating PDB patients in Japan. First, the literature for all case reports in Japan published between January 1990 and December 2002 was reviewed to determine who was diagnosing and treating PDB in Japan. This literature review for all case reports in Japan revealed that 72.1% of cases in Japan were reported from departments of orthopedic surgery. A nationwide two-phase mail survey was conducted for the departments of orthopedic surgery of 2,320 general hospitals accredited by the Japanese Orthopaedic Association. Phase 1 involved determining how many patients with PDB were followed at each hospital. If the answer was one or more, phase 2 of the survey gathered information on the clinical presentation of current patients. The mail survey yielded a final response rate of 75.4% for phase 1 and 87.6% for phase 2. Phase 1 indicated that the prevalence of PDB in Japan is about 2.8 cases per million capita. Phase 2 revealed a slight female predominance, lower frequency of familial clustering, higher frequency of femoral fracture in the affected femur, and a higher ratio of symptomatic PDB in Japan compared with findings in countries displaying a higher prevalence of PDB. The present epidemiological study revealed that the disorder is extremely rare in Japanese individuals, and that some differences exist with regard to the clinical features of PDB between Japanese patients and patients from high-prevalence countries.
    Journal of Bone and Mineral Metabolism 02/2006; 24(3):186-90. DOI:10.1007/s00774-005-0670-z · 2.46 Impact Factor
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    ABSTRACT: A number of prospective studies in the USA and Europe have demonstrated that quantitative ultrasound (QUS) measurements predict fracture risk. To our knowledge, there has been no such study in a Japanese population, and very few studies have measured the prognostic value of QUS measurements among men, even in the USA and Europe. We performed a three-center prospective study to investigate the relationship between baseline heel QUS measurements and non-spine fracture risk. There were 4,028 subjects (1,004 men and 3,024 women), 67.5+/-8.9 years [mean +/- standard deviation (SD)] of age), who underwent heel QUS (Achilles device) at three centers between 1993 and 2000. In 2002, the subjects were mailed a standardized questionnaire that asked about their history of fracture. The mean follow-up period was approximately 5 years. The Achilles measured speed of sound (SOS) and broadband ultrasound attenuation (BUA). We used Cox regression analysis to determine the hazard ratio (HR), using weighted coefficients. SOS, BUA, and stiffness index (SI) predicted self-reported hip, wrist, and total non-spine fractures. After we had adjusted for age, gender, and weight, the HRs of total non-spine fracture were 1.54 [95% confidence interval (CI) 1.39-1.69], 1.53 (1.37-1.70), and 1.80 (1.62-1.98) for 1 SD decrease in SOS, BUA, and SI, respectively. In men, SOS and SI also predicted total non-spine fractures with HRs similar to those in women. The HR of prediction for hip fracture by SOS and SI was better in the short term than in the long term, and the prediction for hip, wrist, and non-spine fracture remained significant between 5 to 10 years of follow-up. Measurements obtained from heel QUS predicted non-spine fracture in Japanese men and women, and the HRs of Japanese of both genders was similar to the risk ratio (RR) of Caucasian men and women. QUS parameters can predict hip, wrist, and non-spine fracture up to 10 years.
    Osteoporosis International 01/2006; 16(12):2107-12. DOI:10.1007/s00198-005-2008-z · 4.17 Impact Factor

  • Journal of Bone and Mineral Metabolism 02/2005; 23(2):97-104. DOI:10.1007/s00774-004-0547-6 · 2.46 Impact Factor
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    ABSTRACT: Fibroblast growth factor (FGF)-23 is a recently identified circulating factor which causes renal phosphate wasting disorders. Although the mechanism of regulation of FGF-23 secretion is unknown, plasma FGF-23 level may be regulated or affected by serum phosphate levels because of its hypophosphatemic effect. We tested the hypothesis that plasma FGF-23 levels may be increased in hyperphosphatemia in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. We measured plasma FGF-23 levels in 158 male uremic patients on maintenance hemodialysis. Plasma samples were obtained before starting dialysis sessions to determine FGF-23 levels by enzyme-linked immunosorbent assay (ELISA). Plasma FGF-23 level exhibited significant and positive correlations with inorganic phosphate, intact parathyroid hormone (PTH), corrected calcium, and duration of hemodialysis on simple regression analyses. All these associations remained significant in multiple regression analyses. Serum phosphate, calcium, and intact PTH could be regulators of FGF-23 levels in uremic patients on maintenance hemodialysis. Our results may provide new insights into the pathophysiologic effects of FGF-23 on calcium-phosphate homeostasis.
    Kidney International 06/2004; 65(5):1943-6. DOI:10.1111/j.1523-1755.2004.00604.x · 8.56 Impact Factor
  • Shinichi Saito · Kiyoshi Nakatsuka ·

    Nippon rinsho. Japanese journal of clinical medicine 03/2004; 62 Suppl 2:358-62.
  • Yoshiki Nishizawa · Kiyoshi Nakatsuka ·

    Nippon rinsho. Japanese journal of clinical medicine 03/2004; 62 Suppl 2:325-32.
  • Kiyoshi Nakatsuka · Takami Miki · Hiroshi Naka · Masaaki Inaba · Yoshiki Nishizawa ·

    Journal of Bone and Mineral Metabolism 02/2004; 22(2):153-8. DOI:10.1007/s00774-003-0464-0 · 2.46 Impact Factor
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    ABSTRACT: The Bio-Intact parathyroid hormone (1-84) assay (Bio-PTH), a newly developed two-site immunochemiluminometric assay, measures exclusively PTH (1-84) in contrast to second-generation "intact PTH" (I-PTH) assays. We investigated the technical performance and clinical significance of this new assay. PTH was measured simultaneously by the Bio-PTH assay and Allegro intact PTH IRMA in sera from Japanese patients with calcium disorders. Measured Bio-PTH in serum was unaffected by six freeze-thaw cycles and was stable at 4 degrees C for 7 days and during storage at -20 or -80 degrees C over 28 days. The calibration curve was linear to 1800 ng/L. The detection limit was 3.9 ng/L. The intra- and interassay imprecision was <2.8% and 3.5%, respectively, for analyte concentrations spanning the range of the calibration curve. Bio-PTH was unaffected by a 1000-fold excess of PTH (7-84), although I-PTH reacted equally with PTH (7-84) and PTH (1-84). Bio-PTH was correlated with I-PTH in healthy individuals (r = 0.953; P <0.0001; n = 26) and in the full population without renal dysfunction (r = 0.994; P <0.0001; n = 62). In 72 volunteers, mean (SD) Bio-PTH was 22.2 (7.1) ng/L, or 62% of the mean I-PTH [36.1 (22.3) ng/L]. This ratio was 51% in hemodialysis patients (n = 177). Mean Bio-PTH was high in patients with primary hyperparathyroidism [121 (85) ng/L; n = 18] and hemodialysis patients [102 (104) ng/L; n = 177], low in idiopathic hypoparathyroidism [5.5 (2.8) ng/L; n = 4], and within 2 SD of the mean for healthy controls in Paget disease of the bone [34 (15) ng/L; n = 9] and bone metastasis [24 (12) ng/L; n = 8]. The Bio-PTH assay is sensitive and precise and produces expected results for patients with the studied disorders of calcium metabolism.
    Clinical Chemistry 02/2004; 50(2):385-90. DOI:10.1373/clinchem.2003.026831 · 7.91 Impact Factor
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    ABSTRACT: The newly developed Elecsys Beta-CrossLaps/serum assay measures C-terminal telopeptide of type I collagen and has thus been proposed as a reliable serum marker for bone resorption. We investigated its usefulness for monitoring the therapeutic effect of estrogen replacement therapy on bone turnover and bone mineral density (BMD) in patients with postmenopausal osteoporosis. Serum Beta-CTx decreased by 43.2% +/- 9.2% (mean +/- SD), and 55.1% +/- 7.0% at 3 and 6 months, respectively, after initiation of estrogen replacement therapy (ERT), which was significantly greater than the respective value of urinary excretion of deoxypyridinoline (DPD) (27.8% +/- 4.1%, 34.1% +/- 4.9%, respectively) or pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) assay (14.5% +/- 4.1%, 13.1% +/- 5.0%, respectively). The percent reduction in serum Beta-CTx at 1, 3, and 6 months after initiation of ERT was significantly correlated in a negative manner with the percent increase in spinal BMD at 6 months. Further, ROC analysis to determine the significance of the percent change in bone resorption markers after 3 months of ERT in predicting the gain in spine BMD after 6 months suggested that serum Beta-CTx and urinary DPD might provide a more discriminating indicator than serum ICTP. In conclusion, the findings suggest that the Elecsys Beta-CrossLaps/serum assay provides a sensitive, and thus useful, tool for assessing bone resorption state in Japanese patients.
    Journal of Bone and Mineral Metabolism 02/2004; 22(2):127-31. DOI:10.1007/s00774-003-0460-4 · 2.46 Impact Factor
  • Shinjiro Takata · Natsuo Yasui · Kiyoshi Nakatsuka · Stuart H Ralston ·

    Journal of Bone and Mineral Metabolism 02/2004; 22(6):519-23. DOI:10.1007/s00774-004-0518-y · 2.46 Impact Factor
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    ABSTRACT: In order to evaluate the efficacy and safety of intermittent subcutaneous administration of 1-34 N-terminal peptide of human parathyroid hormone (hPTH 1-34), 100 units of hPTH 1-34 was subcutaneously injected once a week for 1 year in ten patients with primary osteoporsis (one male and nine females) with no qualitative abnormality of the bone according to the results of iliac crest biopsy performed previously, followed by a second biopsy after the end of the 1-year administration. Written consent of the patients for participation in the study was obtained. The mean lumbar bone mineral density (LBMD) definitely increased, by 1.8%, 3.4%, and 4.6% after 12, 24, and 48 weeks of hPTH administration, in accordance with previous clinical studies. Histomorphometric analysis after double-tetracycline labeling was completed in six patients (one male and five females) after the exclusion of those who dropped out because of adverse events unrelated to the test drug, or refusal of continuation. Examination of thin hard-tissue sections revealed no qualitative abnormalities of bone tissue or bone marrow cavity, such as osteomalacia, woven bone, or osteitis fibrosa, precluding the contribution of qualitatively abnormal tissue elements to any changes of LBMD in response to hPTH 1-34 administration. Histomorphometric measurement in the second biopsy revealed a tendency for an increase of bone volume, a significant increase of osteoid surface, and a tendency for an increase in other parameters of bone formation, compared with values obtained in the preadministration biopsy. Indices of two-dimensional microstructure obtained by microfocus computed tomography (CT) and results of node-strut analysis indicated improvement of trabecular continuity. In five patients in whom three-dimensional reconstruction images were analyzed, there were significant increases of bone volume and trabecular thickness, and a significant decrease in the trabecular bone pattern factor, a parameter related to the continuity, suggesting an improvement of the three-dimensional trabcular microstructure. Intermittent weekly subcutaneous injections of hPTH (1-34) for 48 weeks increased trabecular bone volume and improved microstructure, without causing the appearance of abnormal bone elements in primary osteoporosis.
    Journal of Bone and Mineral Metabolism 02/2004; 22(6):569-76. DOI:10.1007/s00774-004-0525-z · 2.46 Impact Factor
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    Kiyoshi Nakatsuka · Yoshiki Nishizawa · Stuart H Ralston ·
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    ABSTRACT: Three different insertion mutations in the TNFRSF11A gene affecting the signal peptide of RANK have been described. An 18-bp duplication at position 84 (84dup18) is associated with the clinical syndrome of familial expansile osteolysis (FEO), whereas a 15-bp duplication at the same site (84dup15) causes the syndrome of expansile skeletal hyperphosphatasia (ESH). Here we report the phenotype of patients harboring a 27-bp duplication at position 75 (75dup27) in RANK. Affected individuals had hearing impairment and tooth loss beginning in the second or third decade. Radiographs of affected bones showed lytic and sclerotic lesions with bony enlargement and deformity. Serum alkaline phosphatase levels were elevated between 2 and 17 times above the normal range. Most patients had pelvic and skull involvement, and all had involvement of the mandible and maxilla. Most patients also had bony enlargement of the small joints of the hands, and one developed hypercalcemia during a period of immobilization. We conclude that the 75dup27 mutation of RANK causes a Paget's disease of bone-like phenotype that is distinct from, but which overlaps with, FEO and ESH. A particularly striking feature was involvement of the mandible and maxilla, but it remains to be seen if this is a specific feature of the 75dup27 mutation until further kindreds with this mutation are reported.
    Journal of Bone and Mineral Research 09/2003; 18(8):1381-5. DOI:10.1359/jbmr.2003.18.8.1381 · 6.83 Impact Factor
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    ABSTRACT: Rheumatoid arthritis (RA) is a major cause of secondary osteoporosis and is frequently associated with both paraarticular and generalized osteoporosis. The present study was designed to investigate the preferential sites of reduction of bone mineral density (BMD), in the early stage of RA, with special emphasis on the differential effect of RA on BMD in trabecular and cortical components. The participants (30 RA patients and 26 healthy participants) were all female with disease duration of less than 1 year. BMD in the radius was measured at 4% (ultradistal site) and 20% (midshaft) to the ulnar length proximal to the end of radius by peripheral quantitative computed tomography. BMD in lumbar spine was measured by dual X-ray absorptiometry and the osteo-sono assessment index (OSI) of the calcaneus by ultrasound. RA patients showed lower BMD preferentially in the trabecular component, but not in cortical bone component of the ultradistal radius than age-matched normal controls. Calcaneus OSI was also significantly reduced. The radial midshaft and lumbar spine did not differ significantly between RA patients and normal controls. Trabecular BMD in the ultradistal radius exhibited negative correlations with serum CRP, ESR, and RF, and calcaneus OSI with M-HAQ score. In conclusion, it was suggested that disease activity of RA and impairment of daily physical activity might be a significant determinant of deterioration of bone structure in paraartciular distal radius and calcaneus, respectively, in early-stage RA patients.
    Osteoporosis International 09/2003; 14(8):683-7. DOI:10.1007/s00198-003-1427-y · 4.17 Impact Factor
  • Kiyoshi Nakatsuka ·
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    ABSTRACT: Global large scaled clinical trials with new generation of bisphosphonates and raloxifene HCl have been carried out under the spirits of EBM. These pharmaceutical agents have been established as their efficacy of reducing osteoporosis related fragility fractures such as vertebral fractures and non vertebral fractures including hip fractures and applied to clinical use also in Japan. Based on results from clinical trials these agents are listed as first lines in clinical guidelines recently proposed overseas.
    Clinical calcium 09/2003; 13(8):1064-9.
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    Journal of Bone and Mineral Research 04/2003; 18(3):410-2. DOI:10.1359/jbmr.2003.18.3.410 · 6.83 Impact Factor

Publication Stats

1k Citations
207.85 Total Impact Points


  • 1997-2009
    • The University of Sheffield
      • Medical School
      Sheffield, England, United Kingdom
  • 1991-2008
    • Osaka City University
      • • Graduate School of Medicine
      • • Department of Metabolism, Endocrinology, and Molecular Medicine
      • • Second Department of Internal Medicine
      Ōsaka, Ōsaka, Japan
  • 1989
    • Hyogo College of Medicine
      • Dialysis Unit
      Nishinomiya, Hyōgo, Japan